Clean Enough, Chapt 3; Primer on Buprenorphine part 2

Physical dependence vs. addiction
Tolerance and withdrawal are signs of ‘physical dependence’ on a substance.  Addiction, on the other hand, is a complicated term that has different meanings in different contexts, but generally refers to an obsession or attachment to a behavior, person, or substance.  Many people mistakenly consider physical dependence and addiction to be the same.  To illustrate the difference, there are many medications that cause physical dependence that are not addictive.  Effexor and Paxil, two common antidepressants, cause physical dependence and have very uncomfortable withdrawal symptoms.  Physical dependence occurs in non-psychiatric medications as well; suddenly stopping some blood pressure medications will cause an upward spike in blood pressure.  Most people are aware of the withdrawal from missing their morning dose of coffee.  Steroids must be tapered when they are discontinued to avoid the risk of hypotension or even shock. 
So what is addiction?  Addiction can be seen in different ways depending on who is looking.  From my perspective (as a psychiatrist), opioid addiction is the mental obsession for opioids.  Addiction is the relationship that the addict has with the drug.  Most people associate ‘addiction’ with a person using large amounts of the substance, but when addiction is understood to be not the taking of the drug but rather the obsession, it is clear that addiction does not even require the presence of the substance to be active.  In fact, addiction is in some ways most active when the substance is NOT present.  I have heard patients say ‘I’m not an alcoholic– I haven’t had a drink in weeks’.  But in AA there is recognition of a condition known as a ‘dry drunk,’ where a person who loves alcohol is not consuming alcohol, but is consciously or unconsciously thirsting like crazy for a drink!  Similarly, an opioid addict may be free of opioids for several days, but will be so obsessed with finding opioids that there is little ability to think about anything else.  So treating addiction requires much more than keeping the person from using drugs.  Successful treatment also includes removing the mental obsession for the substance and removing the relationship with the substance.  I sometimes refer to addiction to a drug as similar to having an unstable boyfriend or girlfriend.  When the realization is finally made that the relationship is toxic, it isn’t enough to stop dating– the phone calls and text messages have to end as well.
Buprenorphine is different
Drugs that bind to receptors can be classified into several categories depending on their effects at those receptors.  At the mu opioid receptor, hydrocodone (Vicodin), oxycodone (Oxycontin, Percocet), methadone, morphine, and meperidine (Demerol) cause increasing stimulation as the concentration of drug is increased. Molecules that have this effect are called ‘agonists.’  Naltrexone and naloxone, on the other hand, block mu receptors without stimulating the receptors.  Molecules with blocking activity are referred to as ‘antagonists’ and are used medically to reverse overdoses or to block opioid effects. Buprenorphine has actions at mu opioid receptors that are between agonist and antagonist molecules, and is classified as a ‘partial agonist’ or ‘agonist-antagonist.’  Buprenorphine stimulates mu receptors to a point, but beyond that point further increases in dose do not cause increased stimulation—the so-called ‘ceiling effect’.  When Suboxone is taken sublingually, the ceiling effect occurs at a buprenorphine dose of about 4 mg.  Beyond this dose buprenorphine becomes an antagonist as well as an agonist, blocking mu receptors and preventing stimulation by other opioids.  This effect of buprenorphine is unique and distinct from the effects of opioid agonists such as methadone.
It is worth pointing out that like many opioids, buprenorphine has effects at opiate receptor subtypes other than the mu receptor.  Buprenorphine is an antagonist at kappa and epsilon receptors, for example.  Actions at other receptors may be responsible for the mood effects of buprenorphine.
Buprenorphine is very potent.  Outside of the United States buprenorphine is used to treat pain in doses as low as 5 micrograms.  A patch formulation of buprenorphine in the UK (BuTrans) releases buprenorphine through the skin at a dose of 5-25 micrograms per hour.   The potency of buprenorphine creates challenges for those who try to taper Suboxone, when they taper down to two mg/day, think that they have made great progress, and assume that the rest of the taper will be a piece of cake.  They instead find that the work of tapering has just begun.